August 24, 2006 -- 一個新研究指出，不論是心因性或者源於動脈，導致急性缺血性中風的血栓之構成均無異。
這是首次進行中風相關血栓的大範圍系統性組織學分析，研究者使用血管內機械粹取方式，從25位急性缺血性中風病患的腦部之中腦動脈和顱內頸動脈取得血塊。
主要研究者、加州大學洛杉磯分校David Geffen醫學院的Victor Marder醫師向Medscape表示，我們發現所有的凝塊都是相同組成成分，那就是血小板-纖維蛋白沉積，有核細胞—中性球和巨噬細胞—的線性集結，大多位在紅血球之中。
該研究登載於2006八月版的中風(Stroke)期刊。
Marder醫師表示，此一發現駁斥了傳統所教導的動脈和心臟的血栓是不同的說法。
【看起來紅紅的】
Marder醫師指出，神經學的原則之一是來自心房的血塊是紅的，因為主要是紅血球組成，而動脈血塊是白的，因為富含血小板；破裂的動脈粥樣硬化斑塊造成的新的動脈栓塞也是富含血小板，我們研究栓塞物質之後發現，無法分辨栓子來自心房或者動脈損傷。
至於紅血球出現在栓子，可能是因為這些物質在到達腦動脈後累積在栓子，就其本身而言，並非栓子本身物質，但他指出這一點還不是十分確定。
從2001年五月到2005年三月，使用Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 系統 (Concentric Medical Inc)從25位（16 位男性、9位女性）急性缺血性中風病患的腦動脈取得血塊，血塊在發生中風症狀後平均六小時內被移除，並經顯微檢查確認。
在組織學分析之前，兩位神經學家各自鑑別血栓的可能來源，心房纖維顫動病患被視為有心臟血栓凝塊，動脈粥樣硬化損傷者被視為屬於動脈血塊。
【小凝塊，大傷害】
此外，栓子的大小用來檢測其最終到達之目標，研究者報告指出只有寬度< 3 mm的栓子可以到達中腦動脈，> 5 mm 的栓子則完全繞過腦循環。
Marder醫師表示，僅只一粒米大小的血塊會造成重大的、致命的中風，但更大的血塊反而不會造成中風，因為無法進入腦血管之中。
栓子實際上無法以其來源分辨，意指它們的形成過程是循相同機制— 可能一開始是動脈損傷，但是過一段時間之後，可能發展成為心臟血塊。
如果來自心臟的栓子包含血小板和纖維蛋白，可以合理推論使用抗凝血劑和抗血小板療法將可能有效。
此發現提供了心源性栓塞使用抗凝血劑和抗血小板療法有效避免腦栓塞之大型臨床試驗的解釋。
【相同但卻不同】
雖然有相同的組成，研究者仍驚訝於每一凝塊所顯現之不同處；Marder醫師表示，他們看起來都大不相同，每一個都有其特徵，這頗令人吃驚。
每一栓子之外觀不同的原因，反映出了栓子形成和成長位置之血流程度。
栓子或者動脈粥樣硬化血塊周圍血流決定了栓子之構造，換句話說，血流改變了凝塊的形狀，造成了他們各自獨特的外觀。
作者們 (來自加州大學洛杉磯分校David Geffen醫學院) 指出，Jeffrey L Saver醫師是Boehringer Ingelheim的次級預防科學建議小組暨發言人，Sidney Starkman醫師是Genentech的科學建議小組，Gary Duckwiler醫師是Concentric Medica的股東及科學小組成員，加州大學是MERCI Retriever 共同專利擁有者。
Thromboembolic Clots Have Same Composition Regardless of Source
By Caroline Cassels
Medscape Medical News
August 24, 2006 — Whether they originate from cardiac or arterial sources, there are no compositional differences in thrombi that cause acute ischemic stroke, a new study has found.
In the first systematic, large-scale, histological analysis of stroke-related thromboemboli, researchers retrieved clots from the middle cerebral artery and the intracranial carotid artery using endovascular mechanical extraction from the brains of 25 patients who had suffered an acute ischemic stroke.
"We found all of the clots were made up of the same components, namely platelet-fibrin deposits, linear collections of nucleated cells — neutrophils and macrophages — and confined areas rich in red cells," principal investigator Victor Marder, MD, from the David Geffen School of Medicine at University of California, Los Angeles, told Medscape.
The study appears in the August 2006 issue of Stroke.
This finding, said Dr. Marder, contradicts traditional teaching that emboli derived from arterial and cardiac sources are distinctly different.
Seeing Red
"One of the tenets of neurology is that clots that come from the atrium are red because they are composed mainly of red cells, while arterial clots are white because they are platelet rich. While a fresh total occlusion of an artery from a ruptured atherosclerotic plaque is platelet rich, we studied embolic material, and according to our findings, could not tell whether the embolus came from the atrium or from a downstream arterial lesion," said Dr. Marder.
As for the red cell clots present on the emboli, it is possible that such material accumulates on an embolus after it reaches the cerebral artery and may not have been part of the embolic material per se. However, he added, this has yet to be shown definitively.
From May 2001 to March 2005 thrombi were retrieved from the cerebral arteries of 25 patients —16 men and 9 women — with acute ischemic stroke using the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) system (Concentric Medical Inc). Clots were removed an average of 6 hours following onset of stroke symptoms and examined microscopically.
Two neurologists independently determined the likely source of the embolus prior to histological analysis. Patients with atrial fibrillation were deemed to have a cardioembolic clot, while the source of those with atherosclerotic lesions was considered to be arterial.
Small Clots, Big Damage
In addition, the size of the embolus appeared to determine its ultimate destination, with investigators reporting that only emboli < 3 mm in width reached the middle cerebral artery, whereas larger emboli > 5 mm bypassed the cerebral circulation entirely.
"You can get a massive, life-threatening stroke from something that's the size of a grain of rice. But large clots don't cause stroke because they can't fit into the opening of the cerebral vessels," said Dr. Marder.
The fact emboli can't be distinguished according to their source of origin means they form, grow, and develop by the same mechanisms — either immediately, as is the case with arterial lesions, or over time, as in the growth and development of cardiac clots.
"If the emboli from the heart contain significant regions of platelets and fibrin, it seems reasonable to conclude that both anticoagulant and antiplatelet therapies would work,” he said.
This finding, added, provides an explanation for large-scale clinical trial results that have shown both antiplatelet and anticoagulant agents are effective in averting cerebral thromboemboli of cardiac origin.
The Same, But Different
Although the same compositionally, the investigators were surprised to see the difference in the appearance of each clot.
"They all looked dramatically different. Every single one had its own signature appearance. It was amazing," said Dr. Marder.
The reason for the distinct appearance of each thromboembolus reflects the turbulent, almost chaotic blood flow at the sites of thrombus formation and growth.
"The local movement of blood around the clot or atherosclerotic plaque determines the structure of the thrombus. In other words, the blood flow shapes the clot, and that is why they don't have a uniform appearance," he said.
The authors (all from the David Geffen School of Medicine at University of California, Los Angeles) disclose that Jeffrey L Saver, MD, served on a scientific advisory board on secondary prevention to Boehringer Ingelheim and serves on a speaker's bureau on secondary prevention for Boehringer Ingelheim. Sidney Starkman, MD, served on a scientific advisory board to Genentech. Gary Duckwiler, MD, serves on a scientific board and owns stock in Concentric Medical. The University of California is a co–patent holder for the MERCI Retriever.
Stroke. 2006;37:2086-2093.
作者：
Caroline Cassels 2007-6-20